KR20030027106A - 젬-치환 알파 ｖ 베타 3 인테그린 길항제 - Google Patents

젬-치환 알파 ｖ 베타 3 인테그린 길항제 Download PDF

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Publication number: KR20030027106A
Authority: KR; South Korea
Prior art keywords: phenyl; alkyl; solution; propoxy; product
Prior art date: 2000-08-30
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

KR10-2003-7003099A

Other languages

English (en)

Korean (ko)

Inventor

칸나이시큐머

유이

푼-루황

챤드라큐머니잘에스.

허프레니엠.

러셀마크에이.

보이스마크엘.

슈레츠맨로리에이.

첸바바라비.

데사이비핀챤드라엔.

나가라잔스리니바산라이

가섹키알란에프.

페닝토마스디.

로저스토마스

웬트존아담

키레비치알버트

왕야핑

Original Assignee

파마시아 코포레이션

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-08-30

Filing date

2001-08-29

Publication date

2003-04-03

2001-08-29 Application filed by 파마시아 코포레이션 filed Critical 파마시아 코포레이션

2003-04-03 Publication of KR20030027106A publication Critical patent/KR20030027106A/ko

Status Withdrawn legal-status Critical Current

Links

239000005557 antagonist Substances 0.000 title description 17
102000008607 Integrin beta3 Human genes 0.000 title 1
108010020950 Integrin beta3 Proteins 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 127
238000000034 method Methods 0.000 claims abstract description 51
108010044426 integrins Proteins 0.000 claims abstract description 33
102000006495 integrins Human genes 0.000 claims abstract description 33
150000003839 salts Chemical class 0.000 claims abstract description 19
230000002401 inhibitory effect Effects 0.000 claims abstract description 12
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
125000000217 alkyl group Chemical group 0.000 claims description 83
-1 isomers Chemical class 0.000 claims description 81
125000003118 aryl group Chemical group 0.000 claims description 57
125000003545 alkoxy group Chemical group 0.000 claims description 47
125000001072 heteroaryl group Chemical group 0.000 claims description 40
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
125000001188 haloalkyl group Chemical group 0.000 claims description 36
229910052757 nitrogen Inorganic materials 0.000 claims description 33
206010028980 Neoplasm Diseases 0.000 claims description 27
229910052739 hydrogen Inorganic materials 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
229920006395 saturated elastomer Polymers 0.000 claims description 26
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 25
229910052717 sulfur Inorganic materials 0.000 claims description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
125000000304 alkynyl group Chemical group 0.000 claims description 21
125000003710 aryl alkyl group Chemical group 0.000 claims description 21
229910052736 halogen Inorganic materials 0.000 claims description 21
150000002367 halogens Chemical class 0.000 claims description 21
125000003342 alkenyl group Chemical group 0.000 claims description 20
125000000753 cycloalkyl group Chemical group 0.000 claims description 20
125000002252 acyl group Chemical group 0.000 claims description 18
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
125000004122 cyclic group Chemical group 0.000 claims description 18
125000005842 heteroatom Chemical group 0.000 claims description 18
125000002950 monocyclic group Chemical group 0.000 claims description 18
229910052760 oxygen Inorganic materials 0.000 claims description 18
230000033115 angiogenesis Effects 0.000 claims description 17
125000004093 cyano group Chemical group *C#N 0.000 claims description 17
125000003282 alkyl amino group Chemical group 0.000 claims description 16
125000000623 heterocyclic group Chemical group 0.000 claims description 15
125000001424 substituent group Chemical group 0.000 claims description 15
125000004001 thioalkyl group Chemical group 0.000 claims description 15
229910005965 SO 2 Inorganic materials 0.000 claims description 14
206010027476 Metastases Diseases 0.000 claims description 13
230000009401 metastasis Effects 0.000 claims description 13
229940124530 sulfonamide Drugs 0.000 claims description 13
150000003456 sulfonamides Chemical class 0.000 claims description 13
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
230000004614 tumor growth Effects 0.000 claims description 12
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 11
125000004442 acylamino group Chemical group 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
208000001132 Osteoporosis Diseases 0.000 claims description 10
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
229910052799 carbon Inorganic materials 0.000 claims description 10
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 10
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
239000002246 antineoplastic agent Substances 0.000 claims description 9
125000004181 carboxyalkyl group Chemical group 0.000 claims description 9
229940127089 cytotoxic agent Drugs 0.000 claims description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
208000037803 restenosis Diseases 0.000 claims description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
241000124008 Mammalia Species 0.000 claims description 8
206010003246 arthritis Diseases 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
230000003211 malignant effect Effects 0.000 claims description 8
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 8
230000015590 smooth muscle cell migration Effects 0.000 claims description 8
208000037147 Hypercalcaemia Diseases 0.000 claims description 7
208000017442 Retinal disease Diseases 0.000 claims description 7
206010038923 Retinopathy Diseases 0.000 claims description 7
150000001336 alkenes Chemical group 0.000 claims description 7
150000001345 alkine derivatives Chemical class 0.000 claims description 7
125000001769 aryl amino group Chemical group 0.000 claims description 7
229910002091 carbon monoxide Inorganic materials 0.000 claims description 7
230000000148 hypercalcaemia Effects 0.000 claims description 7
208000030915 hypercalcemia disease Diseases 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 6
150000003457 sulfones Chemical class 0.000 claims description 6
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 5
125000003368 amide group Chemical group 0.000 claims description 5
125000004103 aminoalkyl group Chemical group 0.000 claims description 5
125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 5
125000004104 aryloxy group Chemical group 0.000 claims description 5
150000001602 bicycloalkyls Chemical group 0.000 claims description 5
150000003857 carboxamides Chemical class 0.000 claims description 5
125000005518 carboxamido group Chemical group 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
125000004993 haloalkoxycarbonyl group Chemical group 0.000 claims description 5
125000004692 haloalkylcarbonyl group Chemical group 0.000 claims description 5
230000001404 mediated effect Effects 0.000 claims description 5
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 5
XYNHCZVSWZBUJW-UHFFFAOYSA-N 2-[1-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methyl]cyclobutyl]acetic acid Chemical compound C=1C=C(OCCCNC=2N=CC=CC=2)C=CC=1CC1(CC(=O)O)CCC1 XYNHCZVSWZBUJW-UHFFFAOYSA-N 0.000 claims description 4
QGIRZMVNVDLIKQ-UHFFFAOYSA-N 3-benzyl-3-methyl-4-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]butanoic acid Chemical compound C=1C=C(OCCCNC=2N=CC=CC=2)C=CC=1CC(CC(O)=O)(C)CC1=CC=CC=C1 QGIRZMVNVDLIKQ-UHFFFAOYSA-N 0.000 claims description 4
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 4
206010003210 Arteriosclerosis Diseases 0.000 claims description 4
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
125000000524 functional group Chemical group 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 4
125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical compound C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 claims description 3
BKIVZWFPVJBFIM-UHFFFAOYSA-N 2-[1-[2-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]ethyl]cyclopentyl]acetic acid Chemical compound C=1C=C(OCCCNC=2N=CC=CC=2)C=CC=1CCC1(CC(=O)O)CCCC1 BKIVZWFPVJBFIM-UHFFFAOYSA-N 0.000 claims description 3
LZYZWYOPJANCRQ-UHFFFAOYSA-N 2-[1-[2-oxo-2-[4-[2-(pyridin-2-ylamino)ethoxy]phenyl]ethyl]cyclopentyl]acetic acid Chemical compound C=1C=C(OCCNC=2N=CC=CC=2)C=CC=1C(=O)CC1(CC(=O)O)CCCC1 LZYZWYOPJANCRQ-UHFFFAOYSA-N 0.000 claims description 3
ZRBWTQPZRQGEIN-UHFFFAOYSA-N 2-[1-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methyl]cyclopentyl]acetic acid Chemical compound C=1C=C(OCCCNC=2N=CC=CC=2)C=CC=1CC1(CC(=O)O)CCCC1 ZRBWTQPZRQGEIN-UHFFFAOYSA-N 0.000 claims description 3
RMKCCAWNOBHOKM-UHFFFAOYSA-N 2-[1-acetyl-3-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methyl]piperidin-3-yl]acetic acid Chemical compound C1N(C(=O)C)CCCC1(CC(O)=O)CC(C=C1)=CC=C1OCCCNC1=CC=CC=N1 RMKCCAWNOBHOKM-UHFFFAOYSA-N 0.000 claims description 3
CXKIDZGPOXBDAO-UHFFFAOYSA-N 2-[[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]methylsulfonyl]acetic acid Chemical compound CNC1=CC=CC(CCOC=2C=CC(CS(=O)(=O)CC(O)=O)=CC=2)=N1 CXKIDZGPOXBDAO-UHFFFAOYSA-N 0.000 claims description 3
KJOMHIMVRRBOKD-UHFFFAOYSA-N 2-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methylsulfonyl]acetic acid Chemical compound C1=CC(CS(=O)(=O)CC(=O)O)=CC=C1OCCCNC1=CC=CC=N1 KJOMHIMVRRBOKD-UHFFFAOYSA-N 0.000 claims description 3
KGMWOJCHZPZNQZ-UHFFFAOYSA-N 3,3-dimethyl-4-[4-[3-(pyridin-2-ylamino)propoxy]phenyl]butanoic acid Chemical compound C1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 KGMWOJCHZPZNQZ-UHFFFAOYSA-N 0.000 claims description 3
WJSYFMVFTAGCMV-UHFFFAOYSA-N 3-methyl-3-[[4-[3-(pyridin-2-ylamino)propoxy]phenyl]methyl]pent-4-enoic acid Chemical compound C1=CC(CC(CC(O)=O)(C)C=C)=CC=C1OCCCNC1=CC=CC=N1 WJSYFMVFTAGCMV-UHFFFAOYSA-N 0.000 claims description 3
FUYKZCRCKXFKSE-UHFFFAOYSA-N 4-[3-bromo-5-fluoro-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound BrC1=CC(CC(C)(CC(O)=O)C)=CC(F)=C1OCCCNC1=CC=CC=N1 FUYKZCRCKXFKSE-UHFFFAOYSA-N 0.000 claims description 3
NTJFQSZAKYMUTQ-UHFFFAOYSA-N 4-[3-cyano-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound N#CC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 NTJFQSZAKYMUTQ-UHFFFAOYSA-N 0.000 claims description 3
BDUHVVJDEXRYOF-UHFFFAOYSA-N 4-[3-ethynyl-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound C#CC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 BDUHVVJDEXRYOF-UHFFFAOYSA-N 0.000 claims description 3
UOACMCWVCLVCAD-UHFFFAOYSA-N 4-[3-fluoro-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound FC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 UOACMCWVCLVCAD-UHFFFAOYSA-N 0.000 claims description 3
KMERJFNZURFHFM-UHFFFAOYSA-N 4-[3-methoxy-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound COC1=CC(CC(C)(C)CC(O)=O)=CC=C1OCCCNC1=CC=CC=N1 KMERJFNZURFHFM-UHFFFAOYSA-N 0.000 claims description 3
AVQDJEHPEYOWKK-UHFFFAOYSA-N 5-(3-carboxy-2,2-dimethylpropyl)-2-[3-(pyridin-2-ylamino)propoxy]benzoic acid Chemical compound OC(=O)C1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 AVQDJEHPEYOWKK-UHFFFAOYSA-N 0.000 claims description 3
229930194542 Keto Natural products 0.000 claims description 3
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
125000004422 alkyl sulphonamide group Chemical group 0.000 claims description 3
125000005038 alkynylalkyl group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000001246 bromo group Chemical group Br* 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
229910001873 dinitrogen Inorganic materials 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000000468 ketone group Chemical group 0.000 claims description 3
150000002596 lactones Chemical class 0.000 claims description 3
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 3
150000003568 thioethers Chemical group 0.000 claims description 3
CFQCUWPAVGKHKO-UHFFFAOYSA-N 3,3-dimethyl-4-[2-(2-phenylethynyl)-4-[3-(pyridin-2-ylamino)propoxy]phenyl]butanoic acid Chemical class C1=C(C#CC=2C=CC=CC=2)C(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 CFQCUWPAVGKHKO-UHFFFAOYSA-N 0.000 claims description 2
UBWUSZNNSDZPBG-UHFFFAOYSA-N 3,3-dimethyl-4-[4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]phenyl]butanoic acid Chemical compound C1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCC1=CC=C(CCCN2)C2=N1 UBWUSZNNSDZPBG-UHFFFAOYSA-N 0.000 claims description 2
SAJQLKDAKITQMK-UHFFFAOYSA-N 4-N-(1,3-oxazol-2-yl)-2-N-pyrimidin-2-yl-3-N-(1,3-thiazol-2-yl)quinoline-2,3,4-triamine Chemical compound N=1C=CSC=1NC=1C(NC=2N=CC=CN=2)=NC2=CC=CC=C2C=1NC1=NC=CO1 SAJQLKDAKITQMK-UHFFFAOYSA-N 0.000 claims description 2
VITTYGWUOFXKLZ-UHFFFAOYSA-N 4-[2-bromo-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound C1=C(Br)C(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 VITTYGWUOFXKLZ-UHFFFAOYSA-N 0.000 claims description 2
BPUDQESXCYUUIZ-UHFFFAOYSA-N 4-[2-cyano-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound C1=C(C#N)C(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 BPUDQESXCYUUIZ-UHFFFAOYSA-N 0.000 claims description 2
HCWTVUOVODBGBH-UHFFFAOYSA-N 4-[2-ethynyl-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound C1=C(C#C)C(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 HCWTVUOVODBGBH-UHFFFAOYSA-N 0.000 claims description 2
NUWKCAMXYJOTPQ-UHFFFAOYSA-N 4-[3-bromo-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound BrC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 NUWKCAMXYJOTPQ-UHFFFAOYSA-N 0.000 claims description 2
IZDGOARRQXXAQG-UHFFFAOYSA-N 4-[3-chloro-4-[3-(pyridin-2-ylamino)propoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound ClC1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCCNC1=CC=CC=N1 IZDGOARRQXXAQG-UHFFFAOYSA-N 0.000 claims description 2
OAWZCVUGQMYXCB-UHFFFAOYSA-N 4-[4-[2-(6-aminopyridin-2-yl)ethoxy]phenyl]-3,3-dimethylbutanoic acid Chemical compound C1=CC(CC(C)(CC(O)=O)C)=CC=C1OCCC1=CC=CC(N)=N1 OAWZCVUGQMYXCB-UHFFFAOYSA-N 0.000 claims description 2
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
GMPKIPWJBDOURN-UHFFFAOYSA-N Methoxyamine Chemical compound CON GMPKIPWJBDOURN-UHFFFAOYSA-N 0.000 claims description 2
MJXJXQKLVRNBTF-UHFFFAOYSA-N N-(1H-imidazol-2-yl)-2-morpholin-4-ylpyridin-3-amine Chemical compound C1COCCN1C1=NC=CC=C1NC1=NC=CN1 MJXJXQKLVRNBTF-UHFFFAOYSA-N 0.000 claims description 2
150000003973 alkyl amines Chemical class 0.000 claims description 2
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 2
125000005265 dialkylamine group Chemical group 0.000 claims description 2
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 2
SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical group NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 claims description 2
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 21
YVHAIVPPUIZFBA-UHFFFAOYSA-N Cyclopentylacetic acid Chemical compound OC(=O)CC1CCCC1 YVHAIVPPUIZFBA-UHFFFAOYSA-N 0.000 claims 2
206010028289 Muscle atrophy Diseases 0.000 claims 2
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 2
239000004952 Polyamide Substances 0.000 claims 1
230000009826 neoplastic cell growth Effects 0.000 claims 1
229920002647 polyamide Polymers 0.000 claims 1
125000004585 polycyclic heterocycle group Chemical group 0.000 claims 1
230000003042 antagnostic effect Effects 0.000 abstract description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 510
239000000243 solution Substances 0.000 description 267
239000000047 product Substances 0.000 description 264
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 244
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 194
235000019439 ethyl acetate Nutrition 0.000 description 178
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 158
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 151
238000006243 chemical reaction Methods 0.000 description 147
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 135
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 123
239000000203 mixture Substances 0.000 description 108
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 100
239000003921 oil Substances 0.000 description 90
235000019198 oils Nutrition 0.000 description 90
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
239000000741 silica gel Substances 0.000 description 71
229910002027 silica gel Inorganic materials 0.000 description 71
239000011541 reaction mixture Substances 0.000 description 68
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
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Classifications

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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D213/73—Unsubstituted amino or imino radicals
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Oncology (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Diabetes (AREA)
Orthopedic Medicine & Surgery (AREA)
Communicable Diseases (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Endocrinology (AREA)
Hematology (AREA)
Obesity (AREA)
Virology (AREA)
Immunology (AREA)
Ophthalmology & Optometry (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Emergency Medicine (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Pyridine Compounds (AREA)

KR10-2003-7003099A 2000-08-30 2001-08-29 젬-치환 알파 ｖ 베타 3 인테그린 길항제 Withdrawn KR20030027106A (ko)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US22918600P	2000-08-30	2000-08-30
US60/229,186		2000-08-30
PCT/US2001/026963 WO2002018340A1 (en)	2000-08-30	2001-08-29	GEM-SUBSTITUTED α v β 3 INTEGRIN ANTAGONISTS

Publications (1)

Publication Number	Publication Date
KR20030027106A true KR20030027106A (ko)	2003-04-03

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Application Number	Title	Priority Date	Filing Date
KR10-2003-7003099A Withdrawn KR20030027106A (ko)	2000-08-30	2001-08-29	젬-치환 알파 ｖ 베타 3 인테그린 길항제

Country Status (16)

Country	Link
EP (1)	EP1313705A1 (xx)
JP (1)	JP2004510708A (xx)
KR (1)	KR20030027106A (xx)
CN (1)	CN1471512A (xx)
AU (1)	AU2001288515A1 (xx)
BR (1)	BR0113671A (xx)
CA (1)	CA2419699A1 (xx)
CZ (1)	CZ2003459A3 (xx)
EA (1)	EA200300226A1 (xx)
IL (1)	IL154496A0 (xx)
MX (1)	MXPA03001759A (xx)
NO (1)	NO20030925L (xx)
NZ (1)	NZ524159A (xx)
PL (1)	PL365729A1 (xx)
WO (1)	WO2002018340A1 (xx)
ZA (1)	ZA200301162B (xx)

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WO2005039485A2 (en) *	2003-08-13	2005-05-06	Chiron Corporation	Gsk-3 inhibitors and uses thereof
MX2007004535A (es) *	2004-10-14	2007-06-08	Pharmacia Corp	Antagonistas de integrinas bifenilicos.
CN101880270B (zh) *	2009-05-07	2012-10-03	上海华升生物科技有限公司	一种制备1,1-环丙烷二甲醇环亚硫酸酯的方法
SI3050878T1 (sl)	2013-09-24	2022-01-31	Fujifilm Corporation	Nova dušik-vsebujoča spojina ali njena sol ali kovinski kompleks le-te
MA57399B1 (fr) *	2019-10-16	2025-06-30	Morphic Therapeutic, Inc.	Inhibition de l'intégrine humaine alpha4beta7

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NZ239846A (en) *	1990-09-27	1994-11-25	Merck & Co Inc	Sulphonamide derivatives and pharmaceutical compositions thereof
JP2000502704A (ja) *	1995-12-29	2000-03-07	スミスクライン・ビーチャム・コーポレイション	ビトロネクチン受容体拮抗物質
US5919792A (en) *	1996-10-30	1999-07-06	Merck & Co., Inc.	Integrin antagonists
JP2002510328A (ja) *	1997-07-25	2002-04-02	スミスクライン・ビーチャム・コーポレイション	ビトロネクチン受容体アンタゴニスト
KR20010024247A (ko) *	1997-09-24	2001-03-26	스튜어트 알. 수터	비트로넥틴 수용체 길항제

2001
- 2001-08-29 BR BR0113671-2A patent/BR0113671A/pt not_active IP Right Cessation
- 2001-08-29 CN CNA018181082A patent/CN1471512A/zh active Pending
- 2001-08-29 EA EA200300226A patent/EA200300226A1/ru unknown
- 2001-08-29 KR KR10-2003-7003099A patent/KR20030027106A/ko not_active Withdrawn
- 2001-08-29 MX MXPA03001759A patent/MXPA03001759A/es not_active Application Discontinuation
- 2001-08-29 EP EP01968257A patent/EP1313705A1/en not_active Withdrawn
- 2001-08-29 WO PCT/US2001/026963 patent/WO2002018340A1/en not_active Ceased
- 2001-08-29 NZ NZ524159A patent/NZ524159A/en unknown
- 2001-08-29 JP JP2002523458A patent/JP2004510708A/ja not_active Withdrawn
- 2001-08-29 CA CA002419699A patent/CA2419699A1/en not_active Abandoned
- 2001-08-29 AU AU2001288515A patent/AU2001288515A1/en not_active Abandoned
- 2001-08-29 PL PL01365729A patent/PL365729A1/xx not_active Application Discontinuation
- 2001-08-29 CZ CZ2003459A patent/CZ2003459A3/cs unknown
- 2001-08-29 IL IL15449601A patent/IL154496A0/xx unknown
2003
- 2003-02-12 ZA ZA200301162A patent/ZA200301162B/xx unknown
- 2003-02-27 NO NO20030925A patent/NO20030925L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
WO2002018340A1 (en)	2002-03-07
CZ2003459A3 (cs)	2003-09-17
EA200300226A1 (ru)	2003-10-30
EP1313705A1 (en)	2003-05-28
JP2004510708A (ja)	2004-04-08
NO20030925L (no)	2003-04-24
CA2419699A1 (en)	2002-03-07
CN1471512A (zh)	2004-01-28
NZ524159A (en)	2004-08-27
ZA200301162B (en)	2004-05-12
AU2001288515A1 (en)	2002-03-13
BR0113671A (pt)	2004-01-06
MXPA03001759A (es)	2004-11-01
PL365729A1 (en)	2005-01-10
IL154496A0 (en)	2003-09-17
NO20030925D0 (no)	2003-02-27

Publication	Publication Date	Title
US7119098B2 (en)	2006-10-10	Heteroarylakanoic acids as intergrin receptor antagonists
NZ507292A (en)	2003-12-19	Heterocyclic glycyl beta-alanine derivatives useful as vitronectin antagonists
AU753230B2 (en)	2002-10-10	Meta-azacyclic amino benzoic acid compounds and derivatives thereof being integrin antagonists
US20040058915A1 (en)	2004-03-25	Compounds containing a bicyclic ring system useful as alpha v beta 3 antagonists
US20020077321A1 (en)	2002-06-20	Cycloalkyl alkanoic acids as integrin receptor antagonists
US6531494B1 (en)	2003-03-11	Gem-substituted αvβ3 antagonists
JP2006514050A (ja)	2006-04-27	インテグリン受容体アンタゴニスト誘導体としてのβ−アミノ酸化合物のＲ異性体
KR20030027106A (ko)	2003-04-03	젬-치환 알파 ｖ 베타 3 인테그린 길항제
US20040024062A1 (en)	2004-02-05	Hydroxy acid integrin antagonists
US6689754B1 (en)	2004-02-10	Heterocyclic glycyl β-alanine derivatives
US6833366B1 (en)	2004-12-21	Dihydrostilbene alkanoic acid derivatives
US20040116472A1 (en)	2004-06-17	Lactone integrin antagonists
US20080064716A1 (en)	2008-03-13	Biphenyl Integrin Antagonists
US6794385B2 (en)	2004-09-21	Benzoxazine derivatives useful as integrin receptor antagonists
US20040043988A1 (en)	2004-03-04	Cycloalkyl alkanoic acids as intergrin receptor antagonists

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Date	Code	Title	Description
2003-02-28	PA0105	International application	Patent event date: 20030228 Patent event code: PA01051R01D Comment text: International Patent Application
2003-04-03	PG1501	Laying open of application
2006-08-30	PC1203	Withdrawal of no request for examination
2006-08-30	WITN	Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid